Host antigen presenting cells (APC) are known to be critical for the induction of graft versus host disease (GVHD) after allogeneic bone marrow transplantation (BMT) but the relative contribution of specific APC subsets remains unclear. We have studied the role of host B cells in GVHD by using B cell deficient (ìMT) mice as bone marrow transplant recipients in a model of CD4 T cell-dependent GVHD to major histocompatibility antigens. We demonstrated that acute GVHD is initially augmented in ìMT recipients relative to wild-type (WT) recipients (mortality: 85% v 44%, P<0.01) and that this was the result of an increase in donor T cell proliferation, expansion and inflammatory cytokine production early after BMT. Recipient B cells were depleted 28-fold at the time of BMT by total body irradiation (TBI) administered 24 hours earlier and we demonstrated that TBI rapidly induced sustained IL-10 generation from B cells but not dendritic cells (DC) or other cellular populations within the spleen. Finally, recipient mice in which B cells were unable to produce IL-10 due to homologous gene deletion developed more severe acute GVHD than recipient mice in which B cells are WT. Thus the induction of interlukin-10 (IL-10) in host B cells during TBI attenuates experimental acute GVHD.
| Identifer | oai:union.ndltd.org:ADTP/265806 |
| Date | January 2008 |
| Creators | Rowe, Vanessa Robyn |
| Publisher | Queensland University of Technology |
| Source Sets | Australiasian Digital Theses Program |
| Detected Language | English |
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